How to deal with missing longitudinal data in cost of illness analysis in Alzheimer’s disease—suggestions from the GERAS observational study

BACKGROUND: Missing data are a common problem in prospective studies with a long follow-up, and the volume, pattern and reasons for missing data may be relevant when estimating the cost of illness. We aimed to evaluate the effects of different methods for dealing with missing longitudinal cost data and for costing caregiver time on total societal costs in Alzheimer's disease (AD). METHODS: GERAS is an 18-month observational study of costs associated with AD. Total societal costs included patient health and social care costs, and caregiver health and informal care costs. Missing data were classified as missing completely at random (MCAR), missing at random (MAR) or missing not at random (MNAR). Simulation datasets were generated from baseline data with 10-40 % missing total cost data for each missing data mechanism. Datasets were also simulated to reflect the missing cost data pattern at 18 months using MAR and MNAR assumptions. Naïve and multiple imputation (MI) methods were applied to each dataset and results compared with complete GERAS 18-month cost data. Opportunity and replacement cost approaches were used for caregiver time, which was costed with and without supervision included and with time for working caregivers only being costed. RESULTS: Total costs were available for 99.4 % of 1497 patients at baseline. For MCAR datasets, naïve methods performed as well as MI methods. For MAR, MI methods performed better than naïve methods. All imputation approaches were poor for MNAR data. For all approaches, percentage bias increased with missing data volume. For datasets reflecting 18-month patterns, a combination of imputation methods provided more accurate cost estimates (e.g. bias: -1 % vs -6 % for single MI method), although different approaches to costing caregiver time had a greater impact on estimated costs (29-43 % increase over base case estimate). CONCLUSIONS: Methods used to impute missing cost data in AD will impact on accuracy of cost estimates although varying approaches to costing informal caregiver time has the greatest impact on total costs. Tailoring imputation methods to the reason for missing data will further our understanding of the best analytical approach for studies involving cost outcomes

A cost–benefit analysis of COVID-19 vaccination in Catalonia

Background: In epidemiological terms, it has been possible to calculate the savings in health resources and the reduction in the health effects of COVID vaccines. Conducting an economic evaluation, some studies have estimated its cost-effectiveness; the vaccination shows highly favorable results, cost-saving in some cases. (2) Methods: Cost–benefit analysis of the vaccination campaign in the North Metropolitan Health Region (Catalonia). An epidemiological model based on observational data and before and after comparison is usedObjectius de Desenvolupament Sostenible::3 - Salut i BenestarObjectius de Desenvolupament Sostenible::3 - Salut i Benestar::3.3 - Per a 2030, posar fi a les epidèmies de la sida, tuberculosi, malària i les malalties tropicals desateses, i com­batre l’hepatitis, les malalties transmeses per l’aigua i altres malalties transmissiblesPostprint (published version

The GERAS Study: A Prospective Observational Study of Costs and Resource Use in Community Dwellers with Alzheimer's Disease in Three European Countries – Study Design and Baseline Findings

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Hydroxychloroquine for Early Treatment of Adults With Mild Coronavirus Disease 2019: A Randomized, Controlled Trial

No effective treatments for coronavirus disease 2019 (COVID-19) exist. We aimed to determine whether early treatment with hydroxychloroquine (HCQ) would be efficacious for outpatients with COVID-19.The authors thank Gerard Carot-Sans, PhD, for providing medical writing support during the revisions of the subsequent drafts of the manuscript; the personnel from the Fights Aids and Infectious Diseases Foundation for their support in administration, human resources and supply chain management; Eric Ubals (Pierce AB) and Òscar Palao (Opentic) for website and database management; Óscar Camps and OpenArms nongovernmental organization for nursing home operations; and Anna Valentí and the Hospital Germans Trias i Pujol Human Resources Department for telephone monitoring. We thank Consorci Sanitari del Maresme, Centre Sociosanitari El Carme, l'Hospital General de Granollers and occupational hazards department of Hospital Germans Trias i Pujol for their contribution with patient enrollment. We are very grateful to Marc Clotet and Natalia Sánchez who coordinated the JoEmCorono crowd-funding campaign. We thank the Hospital Germans Trias Pujol Institutional Review Board and the Spanish Agency of Medicines and Medical Devices for their prompt action for consideration and approvals to the protocol. Financial support. This work was mainly supported by the crowd-funding campaign JoEmCorono (https://www.yomecorono.com/) with contributions from more than 72 000 citizens and corporations. The study also received financial support from Laboratorios Rubió, Laboratorios Gebro Pharma, Zurich Seguros, SYNLAB Barcelona, and Generalitat de Catalunya. Laboratorios Rubió also contributed to the study with the required doses of hydroxychloroquine (Dolquine®). Foundation Dorneur partly funded lab equipment at Irsi-Caixa.Peer reviewe

Effectiveness of organizational interventions to reduce emergency department utilization: a systematic review.

BACKGROUND: Emergency department (ED) utilization has dramatically increased in developed countries over the last twenty years. Because it has been associated with adverse outcomes, increased costs, and an overload on the hospital organization, several policies have tried to curb this growing trend. The aim of this study is to systematically review the effectiveness of organizational interventions designed to reduce ED utilization. METHODOLOGY/PRINCIPAL FINDINGS: We conducted electronic searches using free text and Medical Subject Headings on PubMed and The Cochrane Library to identify studies of ED visits, re-visits and mortality. We performed complementary searches of grey literature, manual searches and direct contacts with experts. We included studies that investigated the effectiveness of interventions designed to reduce ED visits and the following study designs: time series, cross-sectional, repeated cross-sectional, longitudinal, quasi-experimental studies, and randomized trial. We excluded studies on specific conditions, children and with no relevant outcomes (ED visits, re-visits or adverse events). From 2,348 potentially useful references, 48 satisfied the inclusion criteria. We classified the interventions in mutually exclusive categories: 1) Interventions addressing the supply and accessibility of services: 25 studies examined efforts to increase primary care physicians, centers, or hours of service; 2) Interventions addressing the demand for services: 6 studies examined educational interventions and 17 examined barrier interventions (gatekeeping or cost). CONCLUSIONS/SIGNIFICANCE: The evidence suggests that interventions aimed at increasing primary care accessibility and ED cost-sharing are effective in reducing ED use. However, the rest of the interventions aimed at decreasing ED utilization showed contradictory results. Changes in health care policies require rigorous evaluation before being implemented since these can have a high impact on individual health and use of health care resources. Systematic review registration: http://www.crd.york.ac.uk/PROSPERO. Identifier: CRD420111253

Caregiver Burden in Alzheimer's Disease: Differential Associations in Adult-Child and Spousal Caregivers in the GERAS Observational Study

Background/Aims: To examine factors influencing the caregiver burden in adult-child and spousal caregivers of community-dwelling patients with Alzheimer's disease (AD). Methods: Baseline data from the 18-month, prospective, observational GERAS study of 1,497 patients with AD in France, Germany, and the UK were used. Analyses were performed on two groups of caregivers: spouses (n = 985) and adult children (n = 405). General linear models estimated patient and caregiver factors associated with subjective caregiver burden assessed using the Zarit Burden Interview. Results: The caregiver burden increased with AD severity. Adult-child caregivers experienced a higher burden than spousal caregivers despite spending less time caring. Worse patient functional ability and more caregiver distress were independently associated with a greater burden in both adult-child and spousal caregivers. Additional factors were differentially associated with a greater caregiver burden in both groups. In adult-child caregivers these were: living with the patient, patient living in an urban location, and patient with a fall in the past 3 months; in spouses the factors were: caregiver gender (female) and age (younger), and more years of patient education. Conclusion: The perceived burden differed between adult-child and spousal caregivers, and specific patient and caregiver factors were differentially associated with this burden

Determinants of time to institutionalisation and related healthcare and societal costs in a community-based cohort of patients with Alzheimer's disease dementia

Objectives: To examine the costs of caring for community-dwelling patients with Alzheimer’s disease (AD) dementia in relation to the time to institutionalisation. Methods: GERAS was a prospective, non-interventional cohort study in community-dwelling patients with AD dementia and their caregivers in three European countries. Using identified factors associated with time to institutionalisation, models were developed to estimate the time to institutionalisation for all patients. Estimates of monthly total societal costs, patient healthcare costs and total patient costs (healthcare and social care together) prior to institutionalisation were developed as a function of the time to institutionalisation. Results: Of the 1495 patients assessed at baseline, 307 (20.5%) were institutionalised over 36 months. Disease severity at baseline [based on Mini-Mental State Examination (MMSE) scores] was associated with risk of being institutionalised during follow up (p < 0.001). Having a non-spousal informal caregiver was associated with a faster time to institutionalisation (944 fewer days versus having a spousal caregiver), as was each one-point worsening in baseline score of MMSE, instrumental activities of daily living and behavioural disturbance (67, 50 and 30 fewer days, respectively). Total societal costs, total patient costs and, to a lesser extent, patient healthcare-only costs were associated with time to institutionalisation. In the 5 years pre-institutionalisation, monthly total societal costs increased by more than £1000 (€1166 equivalent for 2010) from £1900 to £3160 and monthly total patient costs almost doubled from £770 to £1529. Conclusions: Total societal costs and total patient costs rise steeply as community-dwelling patients with AD dementia approach institutionalisation

Identifying factors of activities of daily living important for cost and caregiver outcomes in Alzheimer's disease

We aimed to obtain a better understanding of how different aspects of patient functioning affect key cost and caregiver outcomes in Alzheimer's disease (AD)

Disease Progression in Mild Dementia due to Alzheimer Disease in an 18-Month Observational Study (GERAS): The Impact on Costs and Caregiver Outcomes

Background/Aims: We assessed whether cognitive and functional decline in community-dwelling patients with mild Alzheimer disease (AD) dementia were associated with increased societal costs and caregiver burden and time outcomes. Methods: Cognitive decline was defined as a ≥3-point reduction in the Mini-Mental State Examination and functional decline as a decrease in the ability to perform one or more basic items of the Alzheimer’s Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) or ≥20% of instrumental ADL items. Total societal costs were estimated from resource use and caregiver hours using 2010 costs. Caregiver burden was assessed using the Zarit Burden Interview (ZBI); caregiver supervision and total hours were collected. Results: Of 566 patients with mild AD enrolled in the GERAS study, 494 were suitable for the current analysis. Mean monthly total societal costs were greater for patients showing functional (+61%) or cognitive decline (+27%) compared with those without decline. In relation to a typical mean monthly cost of approximately EUR 1,400 at baseline, this translated into increases over 18 months to EUR 2,254 and 1,778 for patients with functional and cognitive decline, respectively. The number of patients requiring supervision doubled among patients showing functional or cognitive decline compared with those not showing decline, while caregiver total time increased by 70 and 33%, respectively and ZBI total score by 5.3 and 3.4 points, respectively. Conclusion: Cognitive and, more notably, functional decline were associated with increases in costs and caregiver outcomes in patients with mild AD dementia

Flow of articles through the literature review process.

<p>Flow of articles through the literature review process.</p